Neurons in the fusiform gyrus are fewer and smaller in autism
ABSTRACT Abnormalities in face perception are a core feature of social disabilities in autism. Recent functional magnetic resonance imaging studies showed that patients with autism could perform face perception tasks. However, the fusiform gyrus (FG) and other cortical regions supporting face processing in controls are hypoactive in patients with autism. The neurobiological basis of this phenomenon is unknown. Here, we tested the hypothesis that the FG shows neuropathological alterations in autism, namely alterations in neuron density, total neuron number and mean perikaryal volume. We investigated the FG (analysing separately layers II, III, IV, V and VI), in seven post-mortem brains from patients with autism and 10 controls for volume, neuron density, total neuron number and mean perikaryal volume with high-precision design-based stereology. To determine whether these results were specific for the FG, the same analyses were also performed in the primary visual cortex and in the cortical grey matter as a whole. Compared to controls, patients with autism showed significant reductions in neuron densities in layer III, total neuron numbers in layers III, V and VI, and mean perikaryal volumes of neurons in layers V and VI in the FG. None of these alterations were found in the primary visual cortex or in the whole cerebral cortex. Although based on a relatively small sample of post-mortem brains from patients with autism and controls, the results of the present study may provide important insight about the cellular basis of abnormalities in face perception in autism.
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ABSTRACT: IntroductionCharacterization of the type and topography of structural changes and their alterations throughout the lifespan of individuals with autism is essential for understanding the mechanisms contributing to the autistic phenotype. The aim of this stereological study of neurons in 16 brain structures of 14 autistic and 14 control subjects from 4 to 64 years of age was to establish the course of neuronal nuclear and cytoplasmic volume changes throughout the lifespan of individuals with autism.ResultsOur data indicate that a deficit of neuronal soma volume in children with autism is associated with deficits in the volume of the neuronal nucleus and cytoplasm. The significant deficits of neuronal nuclear and cytoplasmic volumes in 13 of 16 examined subcortical structures, archicortex, cerebellum, and brainstem in 4- to 8-year-old autistic children suggest a global nature of brain developmental abnormalities, but with region-specific differences in the severity of neuronal pathology. The observed increase in nuclear volumes in 8 of 16 structures in the autistic teenagers/young adults and decrease in nuclear volumes in 14 of 16 regions in the age-matched control subjects reveal opposite trajectories throughout the lifespan. The deficit in neuronal nuclear volumes, ranging from 7% to 42% in the 16 examined regions in children with autism, and in neuronal cytoplasmic volumes from 1% to 31%, as well as the broader range of interindividual differences for the nuclear than the cytoplasmic volume deficits, suggest a partial distinction between nuclear and cytoplasmic pathology.Conclusions The most severe deficit of both neuronal nucleus and cytoplasm volume in 4-to 8-year-old autistic children appears to be a reflection of early developmental alterations that may have a major contribution to the autistic phenotype. The broad range of functions of the affected structures implies that their developmental and age-associated abnormalities contribute not only to the diagnostic features of autism but also to the broad spectrum of clinical alterations associated with autism. Lack of clinical improvement in autistic teenagers and adults indicates that the observed increase in neuron nucleus and cytoplasm volume close to control level does not normalize brain function.01/2015; 3(1):2. DOI:10.1186/s40478-015-0183-5
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ABSTRACT: Autism spectrum disorder (ASD) is defined by impaired social interaction and communication accompanied by stereotyped behaviors and restricted interests. Although ASD is common, its genetic and clinical features are highly heterogeneous. A number of recent breakthroughs have dramatically advanced our understanding of ASD from the standpoint of human genetics and neuropathology. These studies highlight the period of fetal development and the processes of chromatin structure, synaptic function, and neuron-glial signaling. The initial efforts to systematically integrate findings of multiple levels of genomic data and studies of mouse models have yielded new clues regarding ASD pathophysiology. This early work points to an emerging convergence of disease mechanisms in this complex and etiologically heterogeneous disorder.Annual Review of Pathology Mechanisms of Disease 01/2015; 10(1):111-144. DOI:10.1146/annurev-pathol-012414-040405 · 22.13 Impact Factor
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ABSTRACT: We investigated the cytoarchitecture of the anterior superior temporal area (TA2) of the postmortem cerebral cortex in 9 subjects with autism and 9 age-matched typically developing subjects between the ages of 13 and 56 years. The superior temporal gyrus is involved in auditory processing and social cognition and its pathology has been correlated with autism. We quantified the number and soma volume of pyramidal neurons in the supragranular layers and pyramidal neurons in the infragranular layers in each subject. We did not find significant differences in the number or volume of supragranular or infragranular neurons in the cerebral cortex of subjects with autism compared to typically developing subjects. This report does not support an alteration of supragranular to infragranular neurons in autism. However, further stereological analysis of the number of cells and cell volumes in specific cortical areas is needed to better establish the cellular phenotype of the autistic cerebral cortex and to understand its clinical relevance in autism. Copyright © 2015. Published by Elsevier Ireland Ltd.Neuroscience Letters 01/2015; 589. DOI:10.1016/j.neulet.2015.01.021 · 2.06 Impact Factor